Coronary artery disease is the number one cause of death in the United States today. Not only does it cause significant mortality, but it wages a tremendous cost in terms of its morbidity. One of the primary clinical manifestations and a significant cause of the morbidity is angina pectoris. A variety of clinical situations are known to induce angina. These include exercise, hypertension, meals, cold, gallbladder disease and micturition. This proposal outlines a series of experiments designed to study these conditions by activating receptors in the stomach, gallbladder, urinary bladder, muscle and skin with both physiologic and pharmacologic methods. The alterations in the cardiovascular system resulting from stimulation of receptors in these organs will then be studied. Specifically, the effects on heart rate, systemic blood pressure, myocardial contractility, cardiac output, phasic circumflex as well as subendocardial and subepicardial myocardial blood flow and regional flows to the kidney, viscera, resting muscle, skin and brain will be determined. To more closely simulate conditions operative in flow limiting coronary artery disease, myocardial blood flow alterations will be studied in both acutely restricted and unrestricted coronary flow conditions during stimulation of receptors located in these organs. The reflex nature of the responses will be tested via afferent nerve section. Through pharmacologic antagonism, the relative importance of the sympathetic and parasympathetic nervous system will be studied. Characterization of the mechanisms involved in activating these reflexes will provide not only greater understanding, but may also suggest possible prophylactic and therapeutic approaches in dealing with coronary artery disease patients who have angina induced by these conditions.